The overall goal of this program is to understand and correct, at the molecular level, genetic diseases affecting cells derived from pluripotent hematopoietic stem cells. We believe that to attain this goal, we must understand basic biological processes that affect hematopoietic stem cell behavior both in vitro and in vivo in a basic science laboratory to clinical trial translational effort. The proposed Center of Excellence in Molecular Hematology (CEMH) membership in this application draws from a group of well funded investigators with a diverse but complementary experience in hematopoiesis and stem cell biology, viral mediated gene transfer, molecular genetics, virology, hematopoietic stem cell transplantation (cord blood, bone marrow, and cytokine/reagent mediated mobilization), neonatology and vascular and developmental biology. This group is highly collaborative and interactive with numerous co-authored publications, as well as funded projects that span basic, translational, and clinical research. The Cores proposed in this CEMH submission have evolved and been adapted to the current needs of this program. These include: Flow Cytometry, Animal, Imaging, and Angeogenesis/Endothelial/Proangiogenic Cores. All Cores will support the basic and translational studies that underlying the mission of the CEMH and will facilitate development of new discoveries into human trials. The program also includes a Pilot and Feasibility Project, to be funded in part through University funds in order to enhance the training of young investigators to enhance their ability to successfully compete for extramural (e.g. NIH) funding. Together, the CEMH represents an important assembly of critical cores needed to continue and enhance the basic work in progress and to put in place, support which we believe will be needed over the next five years. TABLE OF CONTENTS OVERALL DESCRIPTION 2 OVERALL CENTER CRITIQUE 3 CENTER DIRECTOR 5 OVERALL COMMITTEE BUDGET RECOMMENDATIONS 5 OVERALL ACTION 5 SUPPORT TO BE NEGOTIATED 5 RESEARCH BASE... 5 ADMINISTRATIVE CORE: Hal E. Broxmeyer, Ph.D., Edward F. Srour, Ph.D ... 9 CORE 1: FLOW CYTOMETRY SERVICES: Edward F. Srour, Ph.D. ... 10 CORE 2: OPTICAL MICROSCOPY: Kenneth Dunn, Ph.D, Nadia Carlesso, MD, Ph.D. ... 14 CORE 3: EXPERIMENTAL MOUSE RESOURCES: Simon Conway, Ph.D, Karen E. Pollock, Ph.D.... 16 CORE 4: ANGIOGENESIS, ENDOTHELIAL, &PROANGIOGENIC CELLS: Mervin C. Yoder, M.D, Jamie Case, Ph.D..... 18 PILOT AND FEASIBILITY (P&F) PROGRAM: Hal E. Broxmeyer, Ph.D., Edward F. Srour, Ph.D 20 PUBLIC HEALTH RELEVANCE: Members of the proposed Center of Excellence in Molecular Hematology (CEMH) are at the forefront of innovative basic and clinical research in hematopoiesis and stem cell biology. The establishment of a CEMH will undoubtedly advance the research programs of these investigators and enable cutting edge science in defining mechanisms of molecular regulation of hematopoiesis and stem cell fate.